From the Guidelines
Gabapentin is generally considered safer and less neurotoxic than diphenhydramine for long-term PRN use in treating anxiety. According to a recent study published in The Lancet Psychiatry in 2019 1, gabapentinoids, including gabapentin, have a relatively lower risk of dependence and withdrawal symptoms compared to other medications such as opioids and benzodiazepines. Gabapentin, typically started at 100-300mg doses taken as needed up to three times daily (maximum 3600mg/day), works by modulating calcium channels and GABA neurotransmission without significant cognitive impairment when used appropriately.
In contrast, diphenhydramine, while effective short-term at 25-50mg doses, has anticholinergic properties that can cause significant cognitive side effects including memory problems and confusion, particularly concerning in older adults, as noted in a study published in Gastroenterology in 2007 1. Long-term diphenhydramine use has been associated with increased dementia risk, while gabapentin maintains a better cognitive safety profile over extended periods. However, gabapentin requires careful dosing adjustments in kidney disease and may cause sedation, dizziness, and potential physical dependence with prolonged use.
Key considerations for the use of gabapentin and diphenhydramine include:
- Careful dosing adjustments in kidney disease for gabapentin
- Potential for sedation, dizziness, and physical dependence with prolonged gabapentin use
- Anticholinergic properties of diphenhydramine that can cause cognitive side effects
- Increased dementia risk associated with long-term diphenhydramine use
- Importance of medical supervision for both medications, especially when determining their appropriateness for specific anxiety conditions. Neither medication should be abruptly discontinued after extended use.
From the Research
Comparison of Diphenhydramine and Gabapentin for Long-term PRN Use
- There is no direct comparison of Diphenhydramine and Gabapentin for long-term PRN use in the provided studies.
- However, the studies suggest that benzodiazepines, which are sometimes used for anxiety, are not recommended for long-term treatment due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation 2.
- Gabapentin, an anticonvulsant, has been shown to be effective in treating social phobia and may have a better safety profile compared to benzodiazepines 3.
- Diphenhydramine, an antihistamine, is not mentioned in the provided studies as a treatment for anxiety disorders.
- The studies suggest that SSRIs, such as paroxetine, and anticonvulsants, such as pregabalin, may be effective for long-term treatment of anxiety disorders, including generalized anxiety disorder (GAD) and panic disorder (PD) 4.
- Cognitive behavioral therapy (CBT) may also be effective in discontinuing benzodiazepines and managing anxiety disorders 5.
Neurotoxicity and Safety
- Benzodiazepines have been associated with cognitive impairment, physiological dependence, abuse, and withdrawal phenomena 2, 6, 3.
- Gabapentin has been shown to have a better safety profile compared to benzodiazepines, but its long-term effects on cognitive function are not well studied 3.
- Diphenhydramine has anticholinergic properties, which may be associated with cognitive impairment, especially in older adults, but its neurotoxicity and safety profile for long-term PRN use are not well studied in the context of anxiety disorders.
- Further studies are needed to determine the optimal length and/or dosage of medications to minimize the relapse risk and to identify potential predictors of long-term treatment response 4.